The main objectives of the proposed study is to determine the mechanism(s) of action of gaseous anesthetics. Little is known of the means by which these compounds interact with neural tissue, partly because of the complexity of the mammalian brain which has prevented measurements of precise membrane functions from being made under well controlled conditions. Three projects are planned for the renewal period of GM 24936. The first continues the use of molluscan giant neurons as models for the more complex vertebrates CNS and is primarily concerned with details of synaptic transmission. Initial attention will be focused on presynaptic transmitter release as a result of experiments completed during the initial granting period. This project also includes a detailed study of the squid stellate ganglion under conditions of high hydrostatic pressure and anesthetic exposure in order to determine if the cellular basis of pressure reversal may involve changes occurring at interneuronal synapses. The second project will study volatile anesthetics and high pressure on a vertebrate sensory system, the dog trachealis stretch receptors, in an attempt to follow anesthetic induced changes in the afferent firing patterns of this system. The third project, again of inert gas narcosis on adaptation responses in order to calculate the binding energies involved at the anesthetic site. This project is also founded on work completed during the initial granting period. The three projects together will examine the predictions of two general hypotheses of anesthetic action, namely that anesthesia results from a disruption of specific membrane components and the functions they control, and secondly that pressure reversal may occur at the same site as the anesthetic effect.